Several studies indicate abnormalities in the hypothalamic-pituitary-adrenal axis (HPA) during acute opiate withdrawal, but protracted withdrawal has gotten less study. The current study further characterized the 24-hour time course of plasma cortisol levels in heroin-dependent individuals who were abstinent for 10-15 days, which is beyond the 5 days of acute withdrawal, compared to demographically matched healthy controls using samples collected every 3 hours over 24 hours and assessed with radioimmunoassay (RIA). The abstinent heroin-dependent participants had significantly higher plasma cortisol levels nocturnally suggesting a loss of diurnal variation in these heroin subjects.